scholarly journals Efficient Cardiac Differentiation of Human Amniotic Fluid-Derived Stem Cells into Induced Pluripotent Stem Cells and Their Potential Immune Privilege

2020 ◽  
Vol 21 (7) ◽  
pp. 2359
Author(s):  
Yi-Hsien Fang ◽  
Saprina P.H. Wang ◽  
Zi-Han Gao ◽  
Sheng-Nan Wu ◽  
Hsien-Yuan Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Amniotic Fluid ◽  
Mhc Class Ii ◽  
Pluripotent Stem Cells ◽  
Therapeutic Potential ◽  
Troponin T ◽  
Electrophysiological Study ◽  
Cardiac Differentiation ◽  
Specific Marker ◽  
Human Amniotic Fluid

Mature mammalian hearts possess very limited regenerative potential. The irreversible cardiomyocyte loss after heart injury can lead to heart failure and death. Pluripotent stem cells (PSCs) can differentiate into cardiomyocytes for cardiac repair, but there are obstacles to their clinical application. Among these obstacles is their potential for post-transplant rejection. Although human amniotic fluid-derived stem cells (hAFSCs) are immune privileged, they cannot induce cardiac differentiation. Thus, we generated hAFSC-derived induced PSCs (hAFSC-iPSCs) and used a Wnt-modulating differentiation protocol for the cardiac differentiation of hAFSC-iPSCs. In vitro studies using flow cytometry, immunofluorescence staining, and patch-clamp electrophysiological study, were performed to identify the characteristics of hAFSC-iPSC-derived cardiomyocytes (hAFSC-iPSC-CMs). We injected hAFSC-iPSC-CMs intramuscularly into rat infarcted hearts to evaluate the therapeutic potential of hAFSC-iPSC-CM transplantation. At day 21 of differentiation, the hAFSC-iPSC-CMs expressed cardiac-specific marker (cardiac troponin T), presented cardiomyocyte-specific electrophysiological properties, and contracted spontaneously. Importantly, these hAFSC-iPSC-CMs demonstrated low major histocompatibility complex (MHC) class I antigen expression and the absence of MHC class II antigens, indicating their low immunogenicity. The intramyocardial transplantation of hAFSC-iPSC-CMs restored cardiac function, partially remuscularized the injured region, and reduced fibrosis in the rat infarcted hearts. Therefore, hAFSC-iPSCs are potential candidates for the repair of infarcted myocardium.

Abstract 65: Latrophilin-2 is a Specific Cell-surface Marker for Cardiac Progenitor Cells and Specifies Cardiac Lineage Commitment and Development

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Hyun-Jai Cho ◽  
Choon-Soo Lee ◽  
Jin-Woo Lee ◽  
Jung-Kyu Han ◽  
Han-Mo Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Surface ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Cardiac Development ◽  
Cardiac Differentiation ◽  
Specific Cell ◽  
Specific Marker ◽  
Cardiac Progenitor Cells ◽  
Cardiac Lineage

Backgrounds: The identification of a lineage-specific marker plays a pivotal role in understanding developmental process and is utilized to isolate a certain cell type with high purity for the therapeutic purpose. We here report a new cardiac-specific marker, and demonstrate its functional significance in the cardiac development. Methods and Results: When mouse pluripotent stem cells (ES and iPS cells) were stimulated with BMP4, Activin A, bFGF and VEGF, they differentiated into cardiac cells. To screen cell-surface expressing molecules on cardiac progenitor cells compared to undifferentiated mouse iPS and ES cells, we isolated Flk1+/PDGFRa+ cells at differentiation day 4 and performed microarray analysis. Among candidates, we identified a new G protein-coupled receptor, Latrophilin-2 (LPHN2) whose signaling pathway and its effect on cardiac differentiation is unknown. In sorting experiments under cardiac differentiation condition, LPHN2+ cells derived from pluripotent stem cells strongly expressed cardiac-related genes (Mesp1, Nkx2.5, aMHC and cTnT) and exclusively gave rise to beating cardiomyocytes, as compared with LPHN2- cells. LPHN2-/- mice revealed embryonically lethal and huge defects in cardiac development. Interestingly, LPHN2+/- heterozygotes were alive and fertile. For the purpose of cardiac regeneration, we transplanted iPS-derived LPHN2+ cells into the infarcted heart of adult mice. LPHN2+ cells differentiated into cardiomyocytes, and systolic function of left ventricle was improved and infarct size was reduced. We confirmed LPHN2 expression on human iPS and ES cell-derived cardiac progenitor cells and human heart. Conclusions: We demonstrate that LPHN2 is a functionally significant and cell-surface expressing marker for both mouse and human cardiac progenitor and cardiomyocytes. Our findings provide a valuable tool for isolating cardiac lineage cells from pluripotent stem cells and an insight into cardiac development and regeneration.

scholarly journals Human Amniotic Fluid Stem Cells: Therapeutic Potential for Perinatal Patients with Intractable Neurological Disease

2018 ◽  
Vol 67 (4) ◽  
pp. 57-66 ◽  
Author(s):  
Daigo Ochiai ◽  
Hirotaka Masuda ◽  
Yushi Abe ◽  
Toshimitsu Otani ◽  
Marie Fukutake ◽  
...  
Keyword(s):  
Stem Cells ◽  
Amniotic Fluid ◽  
Neurological Disease ◽  
Therapeutic Potential ◽  
Human Amniotic Fluid ◽  
Amniotic Fluid Stem Cells

Human amniotic fluid-derived induced pluripotent stem cells can differentiate into beating ventricular cardiomyocytes

2013 ◽  
Vol 217 (3) ◽  
pp. S97
Author(s):  
Shaun Michael Kunisaki ◽  
Guihua Jiang ◽  
Julie Di Bernardo ◽  
Andre Monteiro da Rocha ◽  
Luis G. Villa-Diaz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Amniotic Fluid ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Amniotic Fluid ◽  
Ventricular Cardiomyocytes ◽  
Induced Pluripotent

Pluripotent stem cells isolated from human amniotic fluid and differentiation into pancreatic β-cells

2009 ◽  
Vol 32 (11) ◽  
pp. 873-876 ◽  
Author(s):  
L. Trovato ◽  
R. De Fazio ◽  
M. Annunziata ◽  
S. Sdei ◽  
E. Favaro ◽  
...  
Keyword(s):  
Stem Cells ◽  
Amniotic Fluid ◽  
Pluripotent Stem Cells ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Human Amniotic Fluid

Therapeutic potential of a distinct population of human amniotic fluid mesenchymal stem cells and their secreted molecules in mice with acute hepatic failure

Gut ◽  
2011 ◽  
Vol 61 (6) ◽  
pp. 894-906 ◽  
Author(s):  
Dimitra S Zagoura ◽  
Maria G Roubelakis ◽  
Vasiliki Bitsika ◽  
Ourania Trohatou ◽  
Kalliopi I Pappa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Amniotic Fluid ◽  
Hepatic Failure ◽  
Therapeutic Potential ◽  
Acute Hepatic Failure ◽  
Distinct Population ◽  
Human Amniotic Fluid

scholarly journals Prenatal Transplantation of Human Amniotic Fluid Stem Cell Could Improve Clinical Outcome of Type III Spinal Muscular Atrophy

2020 ◽  
Author(s):  
Steven W. Shaw ◽  
Shao-Yu Peng ◽  
Ching-Chung Liang ◽  
Tzu-Yi Lin ◽  
Po-Jen Cheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Amniotic Fluid ◽  
Spinal Muscular Atrophy ◽  
Motor Function ◽  
Therapeutic Potential ◽  
Muscular Atrophy ◽  
Human Amniotic Fluid ◽  
Type Iii ◽  
Amniotic Fluid Stem Cell

Abstract BackgroundType III spinal muscular atrophy (SMA) is a single gene disorder affecting motor function in uterus. Several types of stem cells were utilized to ameliorate SMA based on its capability of regeneration and differentiation. Amniotic fluid is an alternative source of stem cells and is safely sampled without ethical issues. Human amniotic fluid stem cell (hAFSC) shared common surface markers of mesenchymal stem cell. Therefore, this study aims to examine the therapeutic potential of hAFSC for SMA. MethodsOur SMA model mice were generated by deletion of exon 7 of Smn gene and knock-in of human SMN2. A total of 16 SMA model mice were injected with 1x105 hAFSC in uterus, and the other 16 mice served as the negative control. Motor function was analyzed by Rotarod maintenance test, tilting test and grasping test every two months. Twelve months after transplantation, all organs were extracted for post-mortem analysis. Engraftment of hAFSC in organs were assessed by flow cytometry and RNA scope. To observe the function of neuromuscular junction, frequency of myocytes, neurons and innervated receptors were estimated by H&E, methylene blue and immunocytochemistry staining. ResultsWith hAFSC transplantation, 15 fetuses from 5 dams survived (15 of 16, 93.75% survival) and showed better performance in all three motor function tests. Higher engraftment frequency in organs were observed in muscle and liver after hAFSC transplantation. Besides, the muscle of SMA mice with hAFSC transplantation expressed much laminin α and PAX-7. Significantly higher frequency of myocytes, neurons and innervated receptors were observed after hAFSC transplantation. ConclusionsIn our study, hAFSC engrafted on neuromuscular organs and improved cellular and behavioral outcomes of SMA model mice. This fetal therapy could preserve the time window and treat in the uterus to avoid irreversible damage.

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